Association between non-alcoholic fatty liver disease and metabolic abnormalities in children with different weight statuses.

OBJECTIVES: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. METHODS: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. RESULTS: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. CONCLUSIONS: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status.

[Epidemiological characteristics of human respiratory syncytial virus in Hubei Province from 2016 to 2023].

Objective: To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023. Methods: ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed. Results: From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) (P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion: SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.

[Analysis of genital chlamydia and gonococcal infections in infertility].

To analyze the infection of chlamydia (CT) and gonorrhea (NG) in female infertility and male infertility population, and to explore the correlation between CT and NG infection and infertility. A case-control study was conducted to retrospectively analyze the specimens submitted by patients from the Third Xiangya Hospital of Central South University from January 2021 to December 2022. The results showed that a total of 32 184 specimens were collected, and the positive rates of CT were 4.41% (1 419/32 184), and positive rats of NG were 1.42% (457/32 184). In the infertility group (n=3 366), 2 987 were females and 379 were males. In the control group (n=3 366), 2 509 were females and 857 were males. The CT positive rate of the infertility group was 13.61% (458/3 366), which was significantly higher than that of the control group 3.30% (111/3 366), and the difference was statistically significant (χ2=4.245, P<0.05), and the NG positive rate of the infertility group was 6.36% (214/3 366), which was significantly higher than that of the control group 0.89% (30/3 366), and the difference was statistically significant (χ2=4.011, P<0.05). A total of 23 992 female genital tract swab specimens were collected, including 2 987 in the infertility group and 2 509 in the control group, and the positive rate of CT in the female infertility subgroup was 10.41% (311/2 987), which was significantly higher than that in the control group 3.75% (94/2 509), the difference was statistically significant (χ2=4.132, P<0.05), and the NG positive rate of 8.73% (261/2 987) in the female infertility subgroup was significantly higher than that in the control group 0.40% (10/2 509), and the difference was statistically significant (χ2=4.242, P<0.05). A total of 8 192 male urine samples were collected, including 379 in the infertility group and 857 in the control group, and the CT positive rate of the male infertility subgroup was 13.72% (52/379), which was significantly higher than that of the control group 3.38% (29/857), and the difference was statistically significant (χ2=5.267, P<0.05), and the positive rate of NG in the male infertility subgroup was 12.66% (48/379), which was significantly higher than that of the control group 0.93% (8/857), and the difference was statistically significant (χ2=4.166, P<0.05). Among the 2 987 female specimens in the infertility group, 1 034 were in the primary infertility subgroup and 1 953 were in the secondary infertility subgroup, and the positive rates of CT were 7.93% (82/1 034) and 15.72% (307/1 953), respectively, and the positive rates of NG were 3.87% (40/1 034) and 8.65% (169/1 953) respectively, and the difference was not statistically significant (χ2=0.185, P>0.05) and (χ2=0.002, P>0.05). In conclusion, the infection rate of genital tract CT and NG is high in the infertility population, CT and NG are recommended as routine examination indicators for eugenics and infertility screening.

[Factors influencing primary patency time of percutaneous transluminal balloon angioplasty for hemodialysis arteriovenous grafts].

Objective: To investigate the factors affecting primary patency time in arteriovenous graft (AVG) patients receiving percutaneous transluminal balloon angioplasty (PTA). Methods: Hemodialysis patients who underwent AVG placement at the First Affiliated Hospital of Chongqing Medical University between February 2018 and December 2021 were included. The factors including age, gender, total duration of AVG use, site of stenosis, degree of stenosis, length of stenosis, residual stenosis, and presence of thrombosis were analyzed, and influencing factors of primary patency time in AVG were determined using a multiple linear regression model. Results: A total of 101 patients who underwent 331 PTA treatments were enrolled, including 35 males and 66 females. The median age of patients undergoing PTA for the first time was 61 (51, 68) years, and the primary patency time after PTA was 5 (3, 10) months. The patients were followed up for (38.5±15.3) months. Multivariable linear regression analysis revealed that severe stenosis at the venous anastomosis and reflux veins (ß=-2.773, 95%CI:-5.440--0.105, P=0.042), female (ß=-2.247, 95%CI:-3.853--0.642, P=0.006), and previous multiple PTA treatments (ß=-0.516, 95%CI:-0.978--0.054, P=0.029) were risk factors for a shorter primary patency time after PTA. Conclusion: Severity of stenosis at the venous anastomosis and reflux veins of the AVG, female, and a history of multiple previous PTA treatments are associated with a shorter primary patency time in AVG patients.

[Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma].

Objective: To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma. Methods: The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model. Results: Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome (HR=8.50,95% CI: 1.679-8.328,P=0.001), serum albumin (HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy (HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions: Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Resveratrol analogues and metabolites selectively inhibit human and rat 11ß-hydroxysteroid dehydrogenase 1 as the therapeutic drugs: structure-activity relationship and molecular dynamics analysis.

Resveratrol is converted to various metabolites by gut microbiota. Human and rat liver 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) are critical for glucocorticoid activation, while 11ß-HSD2 in the kidney does the opposite reaction. It is still uncertain whether resveratrol and its analogues selectively inhibit 11ß-HSD1. In this study, the inhibitory strength, mode of action, structure-activity relationship (SAR), and docking analysis of resveratrol analogues on human, rat, and mouse 11ß-HSD1 and 11ß-HSD2 were performed. The inhibitory strength of these chemicals on human 11ß-HSD1 was dihydropinosylvin (6.91 µM) > lunularin (45.44 µM) > pinostilbene (46.82 µM) > resveratrol (171.1 µM) > pinosylvin (193.8 µM) > others. The inhibitory strength of inhibiting rat 11ß-HSD1 was pinostilbene (9.67 µM) > lunularin (17.39 µM) > dihydropinosylvin (19.83 µM) > dihydroresveratrol (23.07 µM) > dihydroxystilbene (27.84 µM) > others and dihydropinosylvin (85.09 µM) and pinostilbene (>100 µM) inhibited mouse 11ß-HSD1. All chemicals did not inhibit human, rat, and mouse 11ß-HSD2. It was found that dihydropinosylvin, lunularin, and pinostilbene were competitive inhibitors of human 11ß-HSD1 and that pinostilbene, lunularin, dihydropinosylvin, dihydropinosylvin and dihydroxystilbene were mixed inhibitors of rat 11ß-HSD1. Docking analysis showed that they bind to the steroid-binding site of human and rat 11ß-HSD1. In conclusion, resveratrol and its analogues can selectively inhibit human and rat 11ß-HSD1, and mouse 11ß-HSD1 is insensitive to the inhibition of resveratrol analogues.

[Clinicopathological features of metastatic melanoma in effusion cytology of serosal cavity].

Objective: To investigate the clinical, cytomorphology, immunocytochemical and molecular features of metastatic melanoma in serosal cavity effusion. Methods: Cytological specimens of 14 patients with melanoma in the chest and abdomen were collected from 2017 to 2023, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SOX10, S-100 protein, PRAME, BRAF V600E, HMB45, and Melan A were detected by immunocytochemical methods. Fourteen cases were tested for routine antibody combinations, including Claudin4, HEG1, Calretinin, CD68, etc. Four of the patients had biopsy or surgical samples of metastatic solid lesions of primary sites, and further next-generation sequencing (NGS) or amplification refractory mutation system (ARMS)-PCR molecular test was performed. In addition, 30 cases of serosal effusion samples were collected as control groups (10 cases of benign mesothelial cell reactive hyperplasia, 10 cases of mesothelioma, and 10 cases of metastatic lung adenocarcinoma). Results: Among the 14 cases of melanoma, there were 7 males and 7 females, with ages ranging from 35 to 86 years, and an average age of 57 years, there 10 cases aged ≥50 years. The tumor cells in the serosal effusion varied in morphology and degree of atypia. SOX10 was positive in all 14 cases (14/14), S-100 protein was positive in 10 cases (10/14), PRAME was positive in 12 cases (12/14), BRAF V600E was positive in 10 cases (10/14), HMB45 was positive in 12 cases (12/14), and Melan A was positive in 13 cases (13/14). In 4 patients with histological correlation, the cytological and histological expression of SOX10, BRAF V600E, and PRAME was positive in all 4 cases (4/4); S-100 protein was positive in 2 cases (2/4); and HMB45 and Melan A were positive in 3 cases (3/4). Using NGS or ARMS-PCR, missense mutations of BRAF V600E were detected in all 4 patients; TERT promoter mutations was detected in 1 case; and CDKN2A terminating mutations and MSI1 deletion mutations were detected in the other case. SOX10, S-100, HMB45, Melan A, PRAME and BRAF V600E were all negative in 30 control samples of serosal cavity effusion. Conclusion: By observing the morphology of tumor cells, immunocytochemical test of several combination markers, especially the expression of SOX10, BRAF V600E and PRAME, can help to improve the positive diagnosis rate of melanoma in serous cavity effusion.

In Vitro and In Vivo Evaluation of Toxicity of Structurally Different Diamond-Like Carbon Wear Debris in Joint Replacements.

Diamond-like carbon (DLC) wear debris, which is often composed of different types of structures, is generated from DLC-modified artificial joints in the human body, and its biocompatibility evaluation is especially important to prevent wear-debris-induced implant failure. Here, RAW 264.7 macrophages (inflammatory-reaction assay) and primary mouse osteoblasts (osteoblastogenesis assay) were employed to investigate the toxicity of DLC wear particles (DWPs) by evaluation of cell viability and morphology, enzyme-linked immunosorbent assays, and quantitative reverse-transcription polymerase chain reaction (PCR). Relevant histopathological analysis of rat joints was also performed in vivo. We found that DWPs with a relatively high sp2/sp3 ratio (graphite-phase tendency) manifested a higher cytotoxicity and significant inhibition of osteoblastogenesis. DWPs with a relatively low sp2/sp3 ratio (diamond-phase tendency) showed good biocompatibility in vivo. The DWPs exhibiting a low sp2/sp3 ratio demonstrated reduced secretion of TNF-α and IL-6, along with increased secretion of TIMP-1, resulting in the downregulation of MMP-2 and MMP-9 and upregulation of interleukin-10 (IL-10), thereby attenuating the inflammatory response. Moreover, coculturing osteoblasts with DWPs exhibiting a low sp2/sp3 ratio resulted in an elevated OPG/RANKL ratio and increased expression of OPG mRNA. Because of the absence of electrostatic repulsion, DWPs with a relatively low sp2/sp3 ratio enhanced bovine serum albumin adsorption, which favored cellular activities. Cytotoxicity assessment of DWPs can help establish an evaluation system for particle-related joint disease and can facilitate the clinical application of DLC-coated prostheses.

[Meta-analysis of effectiveness evaluation of preventive measures for acute kidney injury in children].

Objective: To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies. Methods: Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA). Results: A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography (OR=0.26, 0.27; 95%CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery (OR=0.43, 0.44; 95%CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI (OR=0.58, 0.52; 95%CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z-curve for balanced solution (cumulative Z=3.38) crossed the TSA monitoring boundary (Z=3.29). Conclusion: Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

[Effects of enriched environments on behavioral development at toddler period of preterm experienced early repeated procedural pain].

Objective: To investigate the effects of enriched environments on behavioral development at toddler period of preterm who had experienced early repeated operative pain. Methods: A cross-sectional study was conducted. A total of 80 high-risk preterm children of 2 years of age, who had experienced repeated pain stimuli in the neonatal intensive care unit (NICU), were enrolled as preterm group from the High-risk Children Clinic of Children's Hospital of Nanjing Medical University from October 2016 to March 2021. Furthermore, 39 full-term healthy children, aged 2 years, who were undergoing routine check-ups during the same period, were selected as the full-term group. The preterm group was further divided into preterm intervention group and preterm non-intervention group based on the implementation of enriched environment interventions. Data of neonatal characteristics from 3 groups were collected. Growth and development indicators at the age of 2 years were measured. Neuropsychological development evaluated by Gesell developmental scale. Behavioral development evaluated by child behavior check list. The salivary cortisol levels in response to novelty (baseline, task, end) were collected. The family environment, including maternal parenting pressure, were evaluated through a survey questionnaire. One-way ANOVA and least significant difference (LSD) tests were used to compare physical development, maternal parenting stress, Gesell neuropsychological development, and behavioral problems among the 3 groups. A repeated-ANOVA and LSD tests were employed to compare the patterns of salivary cortisol secretion. Pearson correlation analysis was used to explore the influencing factors related to neuropsychological and behavioral development and cortisol level. Results: There were 44 cases in the preterm intervention group (17 males, gestational age of (31.3±2.8) weeks), and 36 in the preterm non-intervention group (29 males, gestational age of (32.5±2.6) weeks). The full-term group consisted of 39 children (23 males, gestational age of (39.3±2.1) weeks). At 2 years of age, the height, weight, and head circumference of the preterm intervention group and non-intervention group were all lower than those of the full-term group (all P<0.05).The Gesell developmental schedule showed that the preterm non-intervention group scored all lower in gross motor, fine motor, adaptive, language and personal-social domains compared to the full-term group (91±7 vs. 97±6, 88±9 vs. 94±6, 89±8 vs. 99±8, 84±10 vs. 100±15, 89±7 vs. 95±6), with statistical significance (all P<0.01). The preterm intervention group scored all higher than the preterm non-intervention group in gross motor, fine motor, adaptive and language domains (all P<0.05), with no significant difference compared to the full-term group (all P>0.05). The number of needle painful procedures during hospitalization in NICU of the non-intervention group was negatively correlated to the adaptive development quotient (r=-0.48, P<0.05). Furthermore, the preterm non-intervention group exhibited higher scores in social withdrawal, depression, somatic complaints, aggression, and destructive behaviors compare to the full-term group and preterm intervention group (F=8.07, 5.67, 7.72, 7.90, 7.06; all P<0.05); while the preterm intervention group showed no significant difference compared to full-term group (all P>0.05). Behavioral problems (social withdrawal and depression) in the preterm non-intervention group were positively correlated with maternal parenting stress (r=0.66, 0.50; both P<0.05). In response to novel visual stimuli and cognitive challenges, the preterm non-intervention group had significantly higher salivary cortisol levels compared to the full-term group (P=0.006), which were negatively correlated with the frequency of early painful procedures (r=-0.83, -0.80; both P<0.01). There was no significant difference in cortisol secretion pattern between the intervention group and the full-term group (P=0.772). Conclusion: Enriched environmental interventions can improve neuropsychological development, decrease behavioral problems, and down-regulate consistent high cortisol response to task in preterm infants who have experienced repeated procedural pain in the NICU by the age of 2 years.

[A retrospective study of 96 cases of adrenal metastases].

Objective: To analyze the clinical characteristics, etiological composition, imaging features, and prognosis of adrenal metastases. Methods: This study is a retrospective case series that included 96 patients with pathologically confirmed adrenal metastases who were treated at West China Hospital, Sichuan University, from 2007 to 2017. Clinical features such as sex, age, tumor size, biochemical tests, imaging characteristics, postoperative pathology, treatment methods, and prognosis were collected and analyzed. The prognosis of patients and its influencing factors were analyzed by Kaplan-Meier survival curve and single-factor Cox risk proportional model. Results: Among the 96 included patients, 64 were male and 32 were female, with a median age of 60 years. There were 89 cases of unilateral adrenal metastases, five cases of bilateral metastases, and two cases with unspecified laterality. The median diameter of the metastases was 3.5 cm×2.9 cm, with an average CT value of 31 HU. Thirty-four cases of adrenal hormones were evaluated, and no abnormality was found.The primary tumor sites were as follows: lung (n=36), kidney (n=19), liver (n=12), pancreas (n=7), rectum (n=3), stomach (n=2), and one case each of tumor in the esophagus, skin, thyroid, left maxillary muscle, breast, bladder, cervix, chest wall, and gastrointestinal tract. There were three cases with unknown primary tumors. The most common pathological type was lung adenocarcinoma (20.8%, 20/96), followed by hepatocellular carcinoma (9.4%, 9/96) and high-grade invasive urothelial carcinoma of the kidney (8.3%, 8/96). Thirty-nine cases were diagnosed concurrently with the primary tumor, while 37 cases were diagnosed after the primary tumor, with a median interval of 15 months (range: 2-144 months). There was no significant correlation between the death risk of adrenal metastatic tumor patients and gender, age, and the size of the metastatic tumor (all P>0.05). There were 4 patients with radiotherapy and chemotherapy alone, 19 patients with surgery alone, and 6 patients with combined radiotherapy and chemotherapy. The median overall survival was 1, 3, and 7 years, respectively. Conclusions: Adrenal metastases were mostly diagnosed at the same time as the primary tumor or within 15 months after the diagnosis of the primary tumor. Unilateral metastasis is common. The lungs are the most common primary lesion, followed by the kidney and liver. CT is the preferred method for the diagnosis of adrenal metastases, and the plain CT value is more than 30 HU. The overall prognosis of adrenal metastases is poor. The prognosis was better for patients who underwent surgery combined with radiotherapy and chemotherapy than those who received only surgery or radiotherapy and chemotherapy alone.

A novel micro-capillary discharge plasma jet triggered gas switch.

To reduce the working coefficient and jitter of the three-electrode gas switch used in linear transformer drivers, a novel trigger method that uses a nanosecond pulse in cooperation with the microplasma jet generated by capillary discharge was developed. A microplasma jet was generated by the nanosecond trigger pulse and injected into the follow-up breakdown gap of the gas switch to decrease the working coefficient. The influence of capillary parameters on the development of the microplasma jet was simulated. The results showed that the microplasma jet significantly reduced the breakdown delay time, jitter, and working coefficient. Increasing the capillary length and decreasing the diameter results in better triggered breakdown performance. Furthermore, the gas switch triggered by a positive pulse exhibits a lower breakdown delay and jitter. Combined with the intensified charge coupled device's shooting results, it can be concluded that the microplasma jet has a distinct influence on streamer formation, which is important for improving the working performance of the gas switch.

Age-related T1 mapping, fat fraction, diffusion and perfusion parameters of the lumbar vertebrae in healthy children under 3.0 T MRI.

AIM: Compare the T1 mapping, fat fraction, diffusion and perfusion parameters of the lumbar vertebrae of different age groups to establish normal values for healthy children and observe the trends in these parameters with age. MATERIALS AND METHODS: A total of 146 healthy children (0-14 years) were included in this prospective study and underwent 3.0 T lumbar MRI examination. The study cohort was divided into five age groups (Group A âˆ¼ E) according to development milestones in children. T1 mapping, Dixon and IVIM (intravoxel incoherent motion)sequence images were used to measure the parameters of lumbar vertebrae 2-4. RESULTS: The normal values of each parameter were measured and compared across different age groups. The T1 value was negatively correlated with age (r=-0.619, p<0.001). The fat fraction (FF%) was positively correlated with age (r=0.635, p<0.001). There was a negative correlation between the D value and age (r=-0.406, p<0.001). The D∗ value was positively correlated with age (r=0.54, p<0.001). The f value was positively correlated with age (r=0.775, p<0.001). The inflexion points of the T1 value and FF% curves were at approximately 3 years old (36 months).The inflexion points of the IVIM-related parameter curves were approximately 5 years old (60 months). CONCLUSION: The age-dependent differences in the vertebral body parameters of this pediatric cohort suggest changes in the bone marrow composition and cellular structure of the vertebral body during physiological growth in children. The establishment of normal values of children's lumbar spine can facilitate the clinical study of diseases.

[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

Climbing Fiber Activation Induced by Footshock in the Cerebellar Vermis Lobule IV/V of Freely Moving Mice.

Parallel fibers (PFs) in the cerebellar cortex are involved in a series of coordinated responses in the fear conditioning paradigm induced by footshock. However, whether footshock can activate cerebellar climbing fibers (CFs) remains unclear. In this study, we recorded calcium (Ca2+) activity in CFs by optical fiber photometry in the cerebellar vermis lobule IV/V of freely moving mice with footshock stimulation. We found that the activation of CFs in the lobule IV/V was highly correlated with footshock stimulation but not with the sound stimulation used as a control. This result suggests that afferent information from CFs might be associated with the motor initiation of fear-related behaviors or fear emotion itself. Thus, our results suggest that a characteristic CF signal in the cerebellar cortex might be related to fear processing or footshock-related behaviors (such as startle responses or pain sensation).

[Identification of oxidative stress-related biomarkers in chronic rhinosinusitis with nasal polyps using WGCNA combined with machine learning algorithms].

Objective: To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP. Methods: Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software. Results: Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences (P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion: This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.

[Cell membrane-penetrating capacity of hPP10-Cu, Zn-SOD fusion protein and its antioxidant and anti-inflammatory activity].

OBJECTIVE: To investigate the cell membrane-penetrating capacity of human cell-penetrating peptide hPP10 carrying human antioxidant protein Cu-Zn superoxide dismutase (Cu, Zn-SOD) and assess the antioxidant and anti-inflammatory activity of these fusion proteins. METHODS: The fusion protein hPP10-Cu, Zn-SOD was obtained by genetic engineering and identified by Western blotting. The membrane-penetrating ability of the fusion protein was evaluated by immunofluorescence assay, fluorescence colocalization assay and Western blotting, its SOD enzyme activity was detected using a commercial kit, and its effect on cell viability was assessed with MTT assay. In a HEK293 cell model of H2O2-induced oxidative stress, the effect of hPP10-Cu, Zn-SOD on cell apoptosis was analyzed with flow cytometry and RT-qPCR, and its antioxidant effect was assessed using reactive oxygen species (ROS) assay; its anti-inflammatory effect was evaluated in mouse model of TPA-induced ear inflammation by detecting expression of the inflammatory factors using RT-qPCR, Western blotting and immunohistochemistry. RESULTS: The fusion protein hPP10-Cu, Zn-SOD was successfully obtained. Immunofluorescence assay confirmed obvious membrane penetration of this fusion protein in HEK293 cells, localized both in the cell membrane and the cell nuclei after cell entry. hPP10-Cu, Zn-SOD at the concentration of 5 µmol/L exhibited strong antioxidant activity with minimal impact on cell viability at the concentration up to 10 µmol/L. The fusion protein obviously inhibited apoptosis and decreased intracellular ROS level in the oxidative stress cell model and significantly reduced mRNA and protein expression of the inflammatory factors in the mouse model of ear inflammation. CONCLUSION: The fusion protein hPP10-Cu, Zn-SOD capable of penetrating the cell membrane possesses strong antioxidant and anti-inflammatory activities with only minimal cytotoxicity, demonstrating the value of hPP10 as an efficient drug delivery vector and the potential of hPP10-Cu, Zn-SOD in the development of skincare products.

Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.